NON-NATURAL AMINO ACIDS IN PEPTIDE DRUG DEVELOPMENT

肽药物开发中的非天然氨基酸

• 批准号: 6585217
• 负责人: THOMAS A DIX
• 金额: $ 12.53万
• 依托单位: ARGOLYN BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6585217
• 关键词: aminoacid; biotherapeutic agent; blood brain barrier; drug design /synthesis /production; drug metabolism; laboratory rat; pain; peptide chemical synthesis; peptides; pharmacokinetics

DESCRIPTION (provided by applicant): Argolyn Bioscience Inc. is an early stage biotechnology company that creates novel peptide drugs and diagnostics with greatly improved intrinsic pharmaceutical properties through substitution of non-natural amino acid analogues for arginine (Arg) or lysine (Lys). In proof-of concept studies thus far, application of the Argolyn technology to peptides of therapeutic interest has resulted in dramatic increases in receptor binding, induction of receptor selectivity, blood and plasma stabilization, and delivery through the blood brain barrier (BBB). A key question for our technology is its breadth: can any peptide of biological interest be improved? The Company currently has late-discovery-stage lead candidates in psychosis, pain, and thrombosis; the psychosis and thrombosis leads are being pursued through other STTRs (submitted) and currently active grants. In this proposal, we will use ABS17, our lead candidate in pain, as another vehicle with which to evaluate the robustness of the technology. We propose to evaluate the systemic pharmacokinetics, blood brain barrier access, oral bioavailability, microsomal stability, and preliminary toxicity of ABS17. Completion of the Specific Aims of this proposal, in combination with data already accumulated on this peptide, will "round out" the preclinical work and provide a third peptide candidate on which the Argolyn platform was successfully applied. It will also lead directly into the Phase 2 STTR that will address the technology more generically (immunogenicity, toxicity of the individual non-natural amino acid residues, and model peptides containing them, etc.).

描述(申请人提供)：ArGolyn Bioscience Inc.是一家处于早期阶段的生物技术公司，通过用非天然氨基酸类似物替代精氨酸(Arg)或赖氨酸(Lys)，创造出新的多肽药物和诊断方法，极大地改善了固有的药学特性。到目前为止，在概念验证研究中，将ArGolyn技术应用于具有治疗意义的多肽已导致受体结合、诱导受体选择性、血液和血浆稳定以及通过血脑屏障(BBB)输送的显著增加。我们技术的一个关键问题是它的广度：任何具有生物学意义的肽都能被改进吗？该公司目前在精神病、疼痛和血栓形成方面有处于后期发现阶段的候选线索；精神病和血栓形成线索正在通过其他STR(已提交)和目前正在进行的赠款进行追踪。在这份提案中，我们将使用ABS17，我们在疼痛领域的领先候选者，作为评估该技术的健壮性的另一种工具。我们建议评估ABS17的全身药代动力学、血脑屏障通达性、口服生物利用度、微粒体稳定性和初步毒性。完成这项建议的具体目标，结合已经积累的关于这一多肽的数据，将“完善”临床前工作，并提供第三个候选多肽，成功地应用了Argolyn平台。它还将直接通向第二阶段STTR，该阶段将更笼统地解决该技术(免疫原性、单个非天然氨基酸残基的毒性以及包含它们的模型多肽等)。